title: Beneficial effects of IKKε-deficiency on body weight and insulin sensitivity are lost in high fat diet-induced obesity in mice.
abstract: Activation of the classical IκB kinases (IKKα and IKKβ) was previously shown to contribute to obesity-induced inflammation and insulin resistance. Using knockout mice, we investigated whether the related isoform IKKε plays a similar metabolic role. IKKε(-/-) mice had reduced body weight, leptin levels, as well as higher insulin sensitivity when kept on chow diet. However, inflammatory parameters, measured in liver, adipose tissue and plasma, were either unaltered or showed a trend toward up-regulation (liver NF-κB activity, TNFα and IL-1β expression). Chronic feeding of a high fat diet induced equal obesity and insulin resistance, and similarly induced inflammatory markers, in IKKε(-/-) and wild-type mice, indicating that under high caloric conditions the inflammatory and metabolic effects of IKKε deficiency were overridden. Taken together, our data indicate that IKKε does not have general pro-inflammatory properties in liver and adipose tissue, and suggest that reduced adiposity is the primary mechanism for improved insulin sensitivity in IKKε(-/-) mice on chow diet.
authors.affiliation: Department of Biochemistry and Molecular Biology II, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. l.scheja@uke.uni-hamburg.de
authors.forename: Ludger
authors.initials: L
authors.lastname: Scheja
authors.forename: Barbara
authors.initials: B
authors.lastname: Heese
authors.forename: Klaus
authors.initials: K
authors.lastname: Seedorf
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000235:genetics*; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D051550:I-kappa B Kinase / Q000235:genetics*; D018836:Inflammation Mediators / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000201:enzymology* / Q000209:etiology
chemical_list: D015415:Biomarkers; D004041:Dietary Fats; D018836:Inflammation Mediators; D016328:NF-kappa B; D051550:I-kappa B Kinase